Fenofibrate is a fibrate used in the treatment of endogenous hyperlipidaemias, hypercholesterolaemias and hypertriglyceridaemias in adults. The preparation of fenofibrate is disclosed in U.S. Pat. No. 4,058,552. Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. Also, treatment with fenofibrate results in increases in high-density lipoprotein (HDL) and apoproteins apoAI and apoAII. Prolonged treatment with fenofibrate at the rate of 300 to 400 mg per day makes it possible to obtain a reduction in total cholesterol of 20 to 25% and a reduction in the levels of triglycerides of 40 to 50%. It thus opposes the development of arteriosclerosis. The customary adult fenofibrate dosage is three gelatin capsules per day, each containing 100 mg of fenofibrate. It is known that fenofibrate absorption variations are observed depending on whether the drug was ingested with a high or low fat meal (Atkins J. C. and D. Faulds (1997) Drugs 54(4) 615–633).
Fenofibrate is not soluble in water, which limits its absorption in the gastrointestinal (GI) tract. To remedy this problem, research groups have tried a multitude of strategies. In U.S. Pat. Nos. 4,800,079 and 4,895,726 micronized fenofibrate formulations of are disclosed. In U.S. Pat. No. 6,277,405 the immediate release of micronized fenofibrate in a tablet or in the form of granules inside a capsule is shown. In U.S. Pat. No. 6,074,670 the immediate release of micronized fenofibrate in a solid state is shown. In U.S. Pat. No. 5,880,148 the combination of fenofibrate and vitamin E is discussed, this formulation is claimed to be useful as an antiatheromatous drug and exhibit a synergistic effect in regards to protecting low-density lipoproteins (LDL) from oxidation. In U.S. Pat. No. 5,827,536 the use of diethylene glycol monoethyl ether (DGME) as solubilizer is discussed and an enhancement in bioavailability claimed. In U.S. Pat. No. 5,545,628 the combination of fenofibrate with one or more polyglycolyzed glycerides is disclosed.
To reduce the effect of fatty food on the adsorption of fenofibrate combinations of micronized fibrate and statins have been developed (US patent application publication 20020161032). It is also known that reducing the particle size of fenofibrate reduces the food effect on fenofibrate adsorption.
In order to prepare the solid formulations of Fenofibrate, the compound is normally dissolved in a proper solvent or solubilizers. Fenofibrate is known to be soluble in many different solubilizers, including anionic (e.g. SDS) and non-ionic (e.g. Triton X-100) surfactants, complexing agents (N-methyl pyrrolidone) (Temeljotov et al (1995) Farmacevtski Vestnik (Slovenia), 46/(Special Issue)).
The technology developed to increase the bioavailability of fenofibrate includes elements and process steps that increase the cost of production making them commercially unattractive. If a formulation for the use fenofibrate and its method of preparation of said formulation could be simplified while increasing the bioavailability of fenofibrate, the resulting product would satisfy an existing need in this field. The present invention provides such a product, a liquid or semi-solid formulation with improved bioavailability for oral administration of fenofibrate or fenofibrate derivatives wherein the particle size of the active agent is not critical to the bioavailability of the product.